Ray Peat on lactic acid

"When metabolic energy is failing, as in hypothyroidism, muscles become easily fatigued, and take up excess water, and the barrier structure is loosened, allowing macromolecules and ATP and other metabolites to leak out, while extraneous substances enter. Typical muscle enzymes such as lactate dehydrogenase and creatine kinase appear in the bloodstream in typical hypothyroid myopathy, and heart proteins, including a particular form of lactic dehydrogenase and a muscle protein, troponin, appear in the blood after a heart stress or fatigue combined with hypothyroidism or systemic inflammation."

- September 2019 - Ray Peat's Newsletter

"Aerobic glycolysis, the metabolism characteristic of cancer, in which lactic acid is produced from glucose despite the presence of oxygen, is promoted by serotonin"

- September 2019 - Ray Peat's Newsletter

"The age pigment, ceroid or lipofuscin, that’s derived largely from PUFA and associated with the macrophage foam cells in the plaque, accumulates iron (Lee, et al, 1998), and by catalyzing oxidation, creates local hypoxia, leading to lactic acid production, contributing to an inflammatory process. The products of lipid peroxidation, such as azelaic acid (Riad, et al., 2018), along with lactate, lead to the calcification of tissue."

- September 2018 - Ray Peat's Newsletter

"Elevated blood lactic acid is one sign of tissue hypoxia. Edema, hypoglycemia, and lactic acidemia can also be produced by other respiratory defects, including hypothyroidism, in which the tissue does not use enough oxygen the skin will be bluer (in thin places, such as around the eyes) when hypoxia, rather than low oxygen consumption, is involved."

- Nutrition For Women

"A response to stimulation is the production of more energy, with a proportional increase of oxygen and sugar consumption by the stimulated tissue; this produces more carbon dioxide, which enlarges the blood vessels in the area, providing more sugar and oxygen. If the irritation becomes destructive, efficiency is lost: oxygen is either consumed wastefully, causing blueness of the tissue (assuming circulation continues; blueness can aiso indicate bad circulation), or is not consumed, causing redness of the tissue. As more sugar is consumed in compensation, lactic acid also enlarges the blood vessels."

- Nutrition For Women

"But a large inflammation, or profound exhaustion, will lower the blood sugar systemically, and will deliver large amounts of lactic acid to the liver. The liver synthesizes glucose from the lactic acid, but at the expense of about 6 times more energy than is obtained from the inefficient metabolism — so that organismically, that tissue becomes 90 times less efficient than its original state. Besides this, an idle destruction of energy molecules (ATP or creatine phosphate) will increase the wastefulness even more."

- Nutrition For Women

"When the organism detects the inflammation or other stress (possibly by sensing changes in blood sugar, lactic acid, or carbon dioxide, or all of them) its adrenal glands will secrete anti-stress hormones, including adrenalin and cortisone (assuming these glands are not exhausted or starved). Both adrenalin and cortisone can raise blood sugar to meet the increased need."

- Nutrition For Women

"Sugar wastage, leading to lactic acid production, can result from a vitamin B2 deficiency, and lactic acid appears to stimulate vascularization"

- Nutrition For Women

"Lactate is a sufficient stimulus to trigger the stress reaction"

- Nutrition For Women

"The relevant effects of thyroid (especially with progesterone, to promote tissue response to thyroid, and to block cortisone production) however, are stimulation of protein synthesis and the prevention of lactate formation - or the stimula tion of its oxidation, either by the tumor itself or by other tissues, to prevent its entry into the Cori cycle, for gluconeogenesis."

- Nutrition For Women

"Lactic acid production (getting out of breath) is the main signal of the need to produce new glucose. Therefore, aerobic exercise is the most stressful."

- Nutrition For Women

"The higher rate of oxygen consumption that occurs at higher body temperature corresponds to a high rate of carbon dioxide production, and an inhibition of lactate formation, with maintenance of a more oxidized balance that reduces inflammation."

- November 2020 - Ray Peat's Newsletter

"At low altitude, when a tissue’s oxygen consumption increases beyond the blood’s ability to deliver oxygen, as in an intensely working muscle, the tissue activates the glycolytic process, converting glucose to lactic acid as a source of additional energy."

- May 2020 - Ray Peat's Newsletter

"Neglecting the role of carbon dioxide in suppressing the formation of lactic acid, they also neglect all of its other essential metabolic effects, including its role as the factor whose absence results in the syndromes of altitude sickness,"

- May 2020 - Ray Peat's Newsletter

"Ignoring that 30 years of slightly elevated lactate might lead to cancer or other degenerative disease, those who taught physiological chemistry also had little interest in the idea of chronic metabolic hyperventilation—losing a little too much CO2 even at sea level."

- May 2020 - Ray Peat's Newsletter

"In a state of chronic stress, oxidative energy production is low, and mediators of inflammation are likely to be chronically increased; there is typically a chronically increased production of lactate, and/or decreased oxidation of it. I"

- May 2020 - Ray Peat's Newsletter

"lactate increases the leakiness of capillaries and loss of fluid, and decreases the ability of oxygen to diffuse from the alveolus to the erythrocyte. Since carbon dioxide diffuses many times more rapidly than oxygen, this diffusion barrier results in low blood CO2 at the same time as hypoxia. Even at sea level, an increase of lactate immediately increases the lungs’ diffusion barrier."

- May 2020 - Ray Peat's Newsletter

"The presence of lactate corresponds to some degree of reductive excess in cells, and the degree of reduction regulates the calcium channels, controlling the excitatory effects of intracellular calcium"

- May 2020 - Ray Peat's Newsletter

"Reduction by stress and/or lactate activates the channels, tightening vascular smooth muscle, and activating a wide range of other cell activities, including inflammation, exosome secretion,"

- May 2020 - Ray Peat's Newsletter

"Antiexcitotoxic substances include progesterone, memantine, minocycline, and agmatine. A high ratio of CO2 to lactate, reducing intracellular pH, is important for preventing excessive excitability. Thyroid hormone, besides directly increasing energy and the CO2/lactate ratio, tends to increase the brain’s temperature, and to increase the ratio of progesterone to estrogen."

- May 2018 - Ray Peats Newsletter

"In childhood and maturity, vigorous oxidative metabolism can maintain some of the essential protective factors of gestation, including adequate levels of glucose and carbon dioxide, good temperature regulation, and avoiding overproduction of superoxide and lactate. In these conditions, the cytokines can contribute to adaptation and continuing development."

- March 2021 - Ray Peat's Newsletter

"For several decades high altitude physiologists have been perplexed by what they call the lactate paradox, the fact that exercise at high altitude, with less oxygen, produces less increase in lactic acid in the blood than it does at sea level, allowing quicker recovery, since it is understood that it is oxidative metabolism that prevents the formation of lactic acid—the lower oxygen availability should lead to a higher lactate content at high altitude, and slower recovery."

- March 2020 - Ray Peat's Newsletter

"Interference with energy production is fundamental to inflammation. When cellular stimulation increases faster than oxygen can be delivered, there is a shift to glycolytic energy production, with the conversion of glucose and amino acids to lactic acid."

- March 2019 - Ray Peat's Newsletter

"Small particles of silica or other inorganic or organic material (such as plastics), can, like radiation, oxygen deprivation, sepsis, or estrogen, increase the production of lactic acid, and this lactate promotes various features of inflammation, including edema, collagen synthesis, and the growth and movement of cells."

- March 2019 - Ray Peat's Newsletter

"The intensity of lipolysis during the night is decreased during the most restorative deep sleep, but the free fatty acids themselves, by blocking oxidation of glucose to carbon dioxide, tend to increase lactate and to depress glucose metabolism, creating an inflammatory and excitatory state that interferes with deep sleep."

- March 2018 - Ray Peat's Newsletter

"Nitric oxide, even in the presence of oxygen, causes a metabolic shift to glycolysis, wastefully producing lactate from glucose"

- March 2017 - Ray Peat's Newsletter

"When stress causes metabolism to shift in the direction of reduction, with lactic acid formation, iron atoms react cyclically with oxygen and the reductants, producing hydroxyl radicals and other very reactive toxins."

- March 2017 - Ray Peat's Newsletter

"Several of these substances inhibit the liberation of free fatty acids and prostaglandin formation, and reduce nitric oxide, lactate production, inflammation, excitation and cholinergic tone, and what they all have in common is supporting a shift away from a highly reduced condition, a shift toward an oxidized-energized balance."

- March 2016 - Ray Peat's Newsletter

"The ideology around stress physiology, falsifying the meaning of serotonin, estrogen, unsaturated fats, sugar, lactate, carbon dioxide, and various other biological molecules, has hidden the simple remedies for most of the inflammatory and degenerative diseases."

- July 2019 - Ray Peat's Newsletter

"In hypothyroidism, with lowered oxidative metabolism, the organism is never far from stress and hyperventilation, with the chronic production of lactate and ammonia. The inefficient metabolism of diabetes has similar effects."

- July 2017 - Ray Peat's Newsletter

"Besides ammonia and lactate, other stress related substances can also increase the drive to breathe more, depleting the essential CO2—endotoxin, acetylcholine, serotonin, hydrogen sulfide, nitric oxide, carbon monoxide, angiotensin, and estrogen, for example."

- July 2017 - Ray Peat's Newsletter

"Hypothyroid people, with low production of CO2, are very susceptible to stress-induced hyperventilation, and they are often in a state of physiological hyperventilation. They are susceptible to over-production of ammonia (De Nardo, et al., 1999; Marti, et al., 1988) and lactate (Zarzeczny, et al., 1996), and to psychosis, especially depression and mania."

- July 2017 - Ray Peat's Newsletter

"Glucose deprivation, by causing glutamine to be used as fuel, increases the formation of ammonia, and ammonia (through an excitatory effect on cells and direct activation of enzymes) promotes the glycolytic use of glucose, producing lactic acid even in the presence of oxygen and perpetuating the scarcity of glucose."

- July 2017 - Ray Peat's Newsletter

"Stress modifies our breathing, causing a vicious cycle, in which the lactate and ammonia produced when stimulation exceeds our oxidative capacity stimulate more intense breathing, causing more carbon dioxide to be lost, reducing oxidative efficiency and increasing the formation of ammonia and lactate."

- July 2017 - Ray Peat's Newsletter

"Because of their role in producing and maintaining pseudohypoxia, and stimulating hyperventilation, there should be more attention to measuring the presence of ammonia and lactate in the blood, breath and urine."

- July 2017 - Ray Peat's Newsletter

"The reduced state leads to increased production of lactate, which produces enough energy to keep the cell alive, but the lactate contributes to the stressed redox shift in the cell that produces it, as well as in the surrounding cells."

- July 2016 - Ray Peat's Newsletter

"When cells are dangerously overstimulated, oxygen and glucose are depleted. In the absence of oxygen, or when the ability to use oxygen is blocked, glucose is converted to lactate, and when glucose is depleted, glutamine is converted to lactate."

- July 2016 - Ray Peat's Newsletter

"With a limited supply of oxygen but an unlimited supply of lactate, the cell’s metabolic reactions are shifted toward a reduced, electronrich, state. This state inhibits the oxidation of glucose by blocking the enzyme pyruvate dehydrogenase, supporting the formation of lactate. These are internal processes of stressed cells, that can be interrupted when the organism provides corrective factors to restore oxidation."

- July 2016 - Ray Peat's Newsletter

"When cancer metabolism increases the amount of lactate in the blood, increased breathing lowers the carbon dioxide in the blood (Gargaglioni, et al., 2003), and the loss of CO2 affects metabolism and physiology at all levels."

- July 2016 - Ray Peat's Newsletter

"he reductive state, resulting from starvation or hypoglycemia, or an excess of lactate or fat, or oxygen deprivation, activates the release of glutamate, and the excitation produced by that can shut off mitochondrial oxidation, reinforcing the state of pseudohypoxia. Nitric oxide synthesis, activated by reductive stress, is a major factor in the suppression of mitochondrial oxidation."

- January 2017 - Ray Peat's Newsletter

"While lactic acid and a more reducing balance in cells activate the excitatory glutamatergic system, an increased concentration of carbon dioxide inhibits that system"

- January 2017 - Ray Peat's Newsletter

"The use of lactate or beta-hydroxybutyrate as metabolic fuel shifts the balance in the reductive direction, the way ethanol metabolism does."

- January 2017 - Ray Peat's Newsletter

"With aging, and during stress, animals metabolism shifts toward reduction, with a higher ratio of lactate to pyruvate, of NADH to NAD, of ascorbate to dehydroascorbate, etc., a state of reductive stress."

- January 2016 - Ray Peat's Newsletter

"t an extreme, the reductive energy derived from aerobic glycolysis can be consumed by the synthesis of fat, permitting glycolysis to proceed, and this can lead to cancer cells that oxidize fatty acids for energy, while converting glucose to fats and lactic acid."

- January 2016 - Ray Peat's Newsletter

"Intense exercise damages cells in ways that cumulatively impair metabolism. There is clear evidence that glycolysis, producing lactic acid from glucose, has toxic effects, suppressing respiration and killing cells. Within_five minutes, exercise lowers the activity of enzymes that oxidize glucose. Diabetes, Alzheimers disease, and general aging involve increased lactic acid production and accumulated metabolic (mitochondrial) damage."

- 2000 - July

"Adaptation to hypoxia or increased carbon dioxide limits the formation of lactic acid. Muscles are 50% more efficient in the adapted state; glucose, which forms more carbon dioxide than fat does when oxidized,, is metabolized more efficiently than fats, requiring less oxygen."

- 2000 - July

"Thyroid hormone, palmitic acid, and light activate a crucial respiratory enzyme, suppressing the formation of lactic acid. Palmitic acid occurs in coconut oil, and is formed naturally in animal tissues. Unsaturated oils have the opposite effect."

- 2000 - July

"Heart failure, shock, and other problems involving excess lactic acid can be treated successfully by poisoning glycolysis with dichloroacetic acid, reducing the production of lactic acid, increasing the oxidation of glucose, and increasing cellular ATP concentration: Thyroid, vitamin B1, biotin, etc., do the same."

- 2000 - July

"While most fatty acids inhibit the oxidation of glucose without immediately inhibiting glycolysis, palmitic acid is unusual, in its inhibition of glycolysis and lactate production without inhibiting oxidation. I assume that this largely has to do with its important function in cardiolipin and cytochrome oxidase."

- 2000 - July

"Exercise, like aging, obesity, and diabetes, increases the levels of circulating free fatty acids and lactate. But ordinary activity of an integral sort, activates the systems in an organized way, increasing carbon dioxide and circulation"

- 2000 - July

"While the flow of carbon dioxide moves from the mitochondrion to the cytoplasm and beyond, tending to remove calcium from the mitochondrion and cell, the flow of lactate and other Organic ions into the mitochondrion can produce calcium accumulation in the mitochondrion, during conditions in which carbon dioxide synthesis, and consequently urea synthesis, are depressed, and other synthetic processes are changed."

- 2000 - July

"Glycolysis produces both pyruvate and lactate, and excessive pyruvate produces almost the same inhibitory effect as lactate; since the Crabtree effect involves nitric oxide and fatty acids as well as calcrum, I think it is reasonable to look for the simplest sort of explanation, instead of trying to experimentally trace all the possible interactions of these substances; a simple physical competition between the products of glycolysis and carbon dioxide, for the binding sites, such as lysine, that would amount to a phase change in the mitochondrion."

- 2000 - July

"In the relative absence of carbon dioxide, or excess of alternative solutes and adsorbents, such as lactic acid, the stability of the mitochondrial phase would be decreased, and the mitochondria would be degraded in both structure and function. As the back side of the idea that carbon dioxide stabilizes and activates mitochondria, the idea that lactic acid is involved in the degrading of mitochondria can also be tested experimentally, and it is already supported by a considerable amount of circumstantial evidence."

- 2000 - July (1)

"Unlike the logical Pasteur effect, the Crabtree effect tends to lower cellular energy and adaptability. Looking at many situations in which increasing the glucose supply increases lactic ~acid production and suppresses respiration, leading to maladaptive decrease in cellular energy, I have begun thinking of lactic acid as a toxin."

- 2000 - July (1)

"When the background of carbon dioxide is high, circulation and oxygenation tend to prevent the anaerobic glycolysis that produces toxic lactic acid, so that a given level of activity will be harmful or helpful, depending on the level of carbon dioxide being produced at rest"

- 2000 - July (1)

"Light promotes glucose oxidation, and is known to activate the key respiratory enzyme. Winter sickness {including lethargy and weight gain), and night stress, have to be included within the idea of the respiratory defect, shifting to the antirespiratory production of lactic acid, and damaging the mitochondria"

- 2000 - July (1)

"Therapeutically, even powerful toxins that block the glycolytic enzymes can improve functions in a varety of organic disturbances associated with (caused by) excessive production of lactic acid. Unfortunately, the toxin that has become standard treatment for lactic acidosis--dichloroacetic acid--is a carcinogen, and eventually produces liver damage and acidosis But several nontoxic therapies can do the same things: Palmitate (formed from sugar under the influence of thyroid hormone, and found in coconut oil), vitamin Bl, biotin, lipoic acid, carbon dioxide, thyroid, naloxone, acetazolamide, for example."

- 2000 - July (1)

"Hypothyroidism suppresses respiration as a source of energy so little carbon dioxide is produced, and lactic acid is formed even when there is no noticeable stress. This in itself resembles hyperventilation, since loss of carbon dioxide is the defining feature of hyperventilation, but the presence of abnormally high adrenergic activity, and of free fatty acids, stimulates further hyperventilation, exacerbating the loss of carbon dioxide. Decreasing the carbon dioxide impairs respiration even more, leading to increased lactic acid production, and that stimulates more adrenergic activity, and so on, in a vicious circle."

- 2000 - January - Ray Peat's Newsletter

"Carbon dioxide limits the electrical depolarization of nerves and muscles, a phenomenon first discovered by Gilbert Ling. This prevents the over-excitation and exhaustion of brain cells and muscle cells, including the heart. The presence of carbon dioxide limits the formation of lactic acid. This explains the lactate paradox of high altitude exertion"

- 1999 - December- Ray Peat's Newsletter

"In Alzheimer’s disease, brain respiratory metabolism is inhibited, creating a carbon dioxide deficiency with an excess of lactic acid and ammonia."

- 1999 - December- Ray Peat's Newsletter

"If excess lactic acid in the brain tissue is characteristic of Alzheimer’s disease and multiple sclerosis, then the lactate paradox suggests that a slightly higher retention of carbon dioxide in the brain of Kashmir residents would counteract chronic excitotoxic effects, suppressing the stress metabolism which leads to the degenerative brain diseases."

- 1999 - December- Ray Peat's Newsletter

"that hypothyroidism, leading to a substitution of lactic acid for carbon dioxide, might contribute to the development of glaucoma by increasing the viscosity of the aqueous humor."

- 1998 - Ray Peat's Newsletter - 3

"The swelling of muscles during hypoxic stress probably represents the basic process, in which lactic acid and pH increase, while CO2is lost."

- 1998 - Ray Peat's Newsletter - 3

"While it is true that the entry of lactic acid into the blood tends to produce metabolic acidosis, the cell which ts producing the lactic acid is actually more alkaline than normal cells. The simplest way to think of it is that acid leaving the muscle makes it less acidic."

- 1998 - Ray Peat's Newsletter - 2

"even though the chemical formula for producing lactic acid directly shows the consumption of acidity, and direct measurements confirm that the cells become more alkaline when they produce lactate, the average biochemist or physiologist ts likely to think the opposite."

- 1998 - Ray Peat's Newsletter - 2

"When I discussed the cellular alkalintzing effect of lactic acid formation in my dissertation in 1972, it wasnt a matter of scientific dispute, and since then, the newer techniques of measurement have made the situation even clearer. But, even today, almost always when conclusions are drawn about muscle fatigue, cancer, radiation damage, etc., they are based to a large extent on the false assumption about lactic acid and cellular pH."

- 1998 - Ray Peat's Newsletter - 2

"During intense contraction, especially when oxygen and carbon dioxide are limited, muscles produce Jactic acid, and the specific reaction in which lactic acid is formed causes protons to be consumed, that ts, it raises the pH."

- 1998 - Ray Peat's Newsletter - 2

"Under all conditions studied, the characteristic lactic acid metabolism of stress and cancer is suppressed at high altitude, as resptration is made more efficient. The Haldane effect shows that carbon dioxide retention 1s increased at high altitude."

- 1998 - Ray Peat's Newsletter - 2

"The Haldane effect is a term for the fact that hemoglobin gives up oxygen in the presence of carbon dioxide, and releases carbon dioxide in the presence of oxygen. It is the increased retention of carbon dioxide that accounts for the lactate paradox."

- 1998 - Ray Peat's Newsletter - 2

"When a state of excitement persists long enough for the cell to produce an excess of lactic acid, causing it to become more strongly charged electrically, nearby blood vessels and nerves will tend to grow into the area, restoring normal energy supply and integrated functioning,"

- 1998 - Ray Peat's Newsletter - 2

"When a cell has been damaged (as by radiation or toxins), its inefficiency creates a small localized distortion im the fields, which will stimulate processes of repair or removal and replacement, as far as the organisms resources allow. When a stress is great enough that the entire organism is exposed to lactic acid, the organism’s adaptive resources are being challenged, and potentially harmful responses are evoked. For example, a sluggish liver can allow the blood lactate concentration to mse during stress, and this can lead to secretion of endorphins and pituitary hormones (Elias, et al, 1997). The endorphins can increase histamine release, and growth hornone increases free fatty acids; increased permeability of blood vessels can allow proteins and fats to leave the blood stream with cumulatively harmful effects."

- 1998 - Ray Peat's Newsletter - 2

"Sodium and carbon dioxide are essential for maintaining the normal fields, and these substances interact in ways that cause both of them to be lost during stress. In hypothyroidism, © sodium is persistently lost, as carbon dioxide is chronically replaced by lactic acid, Both sodium (Veech, et al.; Garrahan and Glynn) and carbon dtoxide--by stimulating the Krebs cycle, and keeping the respiratory enzymes active--help to maintain the normal level of ATP, protecting against stress and shock."

- 1998 - Ray Peat's Newsletter - 2

"In general, lactic acid in the blood can be taken as a sign of defective respiration, since the breakdown of glucose to lactic acid increases to make up for deficient oxidative energy production. Normal aging seems to involve a tendency toward excess lactic acid production, and age-pigment is known to activate the process."

- 1997 - Ray Peat's Newsletter

"Eliminating respiratory toxins (such as unsaturated oils, estrogenic and antithyroid substances, lead, and excess iron) is the most obvious first step to take when there is excess lactic acid formation."

- 1997 - Ray Peat's Newsletter

"Carbon dioxide supplements have been shown experimentally to reduce residual lactate production."

- 1997 - Ray Peat's Newsletter

"It has been found that, during intense exercise (which always produces a lactic acid accumulation in the blood), a lower peak accumulation of lactate occurs at high altitude, and this seems to be caused by a reduction in the rate of glycolysis, or glucose consumption."

- 1997 - Ray Peat's Newsletter

"For more than a century, most physiologists have explained muscle soreness as being caused by lactic acid, while generally ignoring the great swelling of muscles that results from intense exercise."

- 1994 - April - Ray Peat's Newsletter

"Thyroid function is essential to all cell processes, including protein assimilation and synthesis, formation of growth hormone, etc. Without thyroid hormone to sustain respiration, inefficient glycolysis wastes energy; unoxidized lactate provokes catabolism of liver protein. Hypoglycemia stimulates secretion of glucocorticoids, which maintain blood sugar at the expense of rapid catabolism of protein."

- 1989 - November - Ray Peat's Newsletter